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Background: Upper gastrointestinal (UGI) bleed is a common emergency presenting to emergency departments all over the world. Since the spectrum of UGI bleeding varies from region to region, it is important to know the profile of UGI bleed for proper management approach. Here, we present the endoscopic profile of UGI bleed presenting to a tertiary care setting in Northern India. Aims and Objectives: This study aimed to determine the epidemiological and endoscopic profile of patients with UGI over twenty years. Materials and Methods: The retrospective and observational study included adults patients (above 18 years of age) of either gender, who presented with UGI bleed at our center over a twenty year period from January 1999 to December 2018. Results: A total of 13418 patients with UGI bleed had esophagogastroduodenoscopy (EGD) done on them during this period. Six thousand one hundred and thirty-two patients (45.7%) were females while 7285 were males (54.3%). Mean age was 46±16 years. The common endoscopic findings were peptic ulcer disease in 7508 (48.25%) patients followed by erosive gastritis in 2305 (14.81%), UGI tract malignancy in 1152 (7.8%). Variceal bleed was seen in 900 (5.77%) patients. Conclusion: Peptic ulcer related bleed is the most common cause of UGI bleed in our center. Portal hypertension is relatively less frequent a cause of UGI bleed in our place. [ABSTRACT FROM AUTHOR]

There are currently no preventive or disease-modifying therapies for Parkinson's Disease (PD). Failures in clinical trials necessitate a re-evaluation of existing pre-clinical models in order to adopt systems that better recapitulate underlying disease mechanisms and better predict clinical outcomes. In recent years, models utilizing patient-derived induced pluripotent stem cells (iPSC) have emerged as attractive models to recapitulate disease-relevant neuropathology in vitro without exogenous overexpression of disease-related pathologic proteins. Here, we utilized iPSC derived from patients with early-onset PD and dementia phenotypes that harbored either a point mutation (A53T) or multiplication at the α-synuclein/SNCA gene locus. We generated a three-dimensional (3D) cortical neurosphere culture model to better mimic the tissue microenvironment of the brain. We extensively characterized the differentiation process using quantitative PCR, Western immunoblotting and immunofluorescence staining. Differentiated and aged neurospheres revealed alterations in fatty acid profiles and elevated total and pathogenic phospho-α-synuclein levels in both A53T and the triplication lines compared to their isogenic control lines. Furthermore, treatment of the neurospheres with a small molecule inhibitor of stearoyl CoA desaturase (SCD) attenuated the protein accumulation and aberrant fatty acid profile phenotypes. Our findings suggest that the 3D cortical neurosphere model is a useful tool to interrogate targets for PD and amenable to test small molecule therapeutics. [ABSTRACT FROM AUTHOR]

Internet availability and its integration with smart technologies have favored everyday objects and things and offered new areas, such as the Internet of Things (IoT). IoT refers to a concept where smart devices or things are connected and create a network. This new area has suffered from big data handling and security issues. There is a need to design a data analytics model by using new 5G technologies, architecture, and a security model. Reliable data communication in the presence of legitimate nodes is always one of the challenges in these networks. Malicious nodes are generating inaccurate information and breach the user's security. In this paper, a data analytics model and self-organizing architecture for IoT networks are proposed to understand the different layers of technologies and processes. The proposed model is designed for smart environmental monitoring systems. This paper also proposes a security model based on an authentication, detection, and prediction mechanism for IoT networks. The proposed model enhances security and protects the network from DoS and DDoS attacks. The proposed model evaluates in terms of accuracy, sensitivity, and specificity by using machine learning algorithms. [ABSTRACT FROM AUTHOR]

Background: Adherence to antihypertensive therapy is an important factor in determining the clinical course of hypertension. This study was planned to estimate adherence to antihypertensive therapy and its determinants among OPD patients attending two primary care hospitals in Kashmir valley. Methods: This study employed a cross-sectional study design. All subjects who reported to OPD between October and December 2020 and had been prescribed antihypertensive medications for at least 1 year were included. Sociodemographic information was collected on a pretested schedule and adherence to medications was assessed by using the-14 item Hill-Bone HBP Compliance to High Blood Pressure Therapy Scale (HB-HBP). Mann–Whitney test and Spearman's rank correlation coefficient were used. Results: A total of 406 subjects were included in the final analysis with a mean age of 58 years for women and 56 years for men. The sample comprised 54% women. More than 60% of subjects were currently married, urban area residents, and belonged to middle strata of social class. The mean score obtained in the HB-MAS (maximum score 56) was 19.26 (SD ± 4.3). Subjects aged 60 years and above, those belonging to lower socioeconomic class, and subjects prescribed three or more drugs with more than once-daily dosing regimen had higher odds of having poor adherence. Conclusion: There is suboptimal adherence among OPD patients at primary care level. There is a need for enhanced counselling regarding medication adherence particularly for elderly, poor, illiterate persons and those prescribed multiple medicines with more than once-daily dosing. [ABSTRACT FROM AUTHOR]

Objective: To study the frequency of In-Stent Restenosis and its treatment in patients undergoing Percutaneous Coronary Intervention for coronary artery disease. Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Cardiology, Armed Forces Institute of Cardiology & National Institute of Heart disease (AFIC/NIHD) Rawalpindi, from Jul 2017 to Jul 2019. Methodology: All the patients who underwent Percutaneous Coronary Intervention for Coronary Artery Disease at our institute were considered for this study. A consecutive sampling method was used and inclusion/exclusion criteria was applied. Following data was obtained; 1) Demographic information and clinical risk factors like history of hypertension, hyperlipidemia, diabetes mellitus, smoking, coronary artery disease characteristics (number of diseased arteries, bifurcation lesions, calcification, chronic total occlusions-CTO and tortuosity) 3), Stent factors (under expansion, fracture, longitudinal miss, stent gap). Data recording, storage, assessment and analysis was done by using SPSS software version 21. Results: Among 1332 cases, 50 had In-Stent Restenosis with overall prevalence of 3.75%. Mean age of the patients with In-Stent Restenosis was 58.76 (± 9.97), with 45 (90%) male and 5 (10%) female. Diabetes Mellitus was the commonest risk factor (22.9%) followed by Hypertension (18%). Sixty four percent of the patients (n=32) had Single Vessel Coronary Artery Disease, 14 (28%) had Double Vessel Coronary Artery Disease and 4 (8%) had Tripple Vessel Coronary Artery Disease. Left Anterior Descending was the commonest coronary artery that developed In-Stent Restenosis, followed by Right Coronary Artery and Left Circumflex respectively. Previously deployed stents which developed In-Stent Restenosis showed longitudinal geographical miss in 16%, stent under expansion in 6% and stent gap in 4%. There was statistically significant association (p-value=0.02) between stent length and frequency of In-Stent Restenosis and it was commonest in stents longer than 30 mm. Eighty six percent (n=43) of In-Stent Restenosis cases in our study group was treated with Drug Eluting Stent followed by Drug Eluting Balloon in 32% and Plain Old Balloon Angioplasty in 22%. Conclusion: History of diabetes mellitus and greater stent length were major risk factors in developing In-Stent Restenosis in our study. DES was the commonest treatment modality used. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and compare the impact of COVID-19 pandemic on admission rates and mortality in patients presenting with ST elevation myocardial infarction (STEMI) to a tertiary care cardiac setup in Pakistan. Study Design: Comparative cross-sectional study Place and Duration of Study: Armed Forces Institute of Cardiology/National Institute of Heart Disease (AFIC/NIHD) Rawalpindi, from Apr to May 2020. Methodology: All ST elevation myocardial infarction patients presenting to our hospital for two months (April, May) during COVID-19 pandemic were studied. Similar patients were also analyzed from pre-COVID era for an equivalent period. Parameters compared include total number of ST elevation myocardial infarction patients, age, gender, door to balloon (DTB) time, MI type (anterior versus non-anterior) and prognosis in terms of mortality. Categorical variables are presented as absolute numbers and percentages and compared by chi-square test. Odds ratio was determined to study the impact of COVID-19 pandemic on ST elevation myocardial infarction mortality. SPSS-23 was used for all the analysis. Results: We observed a significant 43% reduction in the total numbers of ST elevation myocardial infarction admissions compared to equivalent time before pandemic. There was a decrease in patients >75 years of age (4.1%, p-value 0.007), decrease in female patients (21.7%, p-value 0.001), mild improvement in door to balloon (1.3%, p-value 0.4), increase in anterior MI (1.2%, p-value 0.7). The ST elevation myocardial infarction case fatality rate during the pandemic increased from 4-7.1% (Odds ratio 1.81, confidence interval 1.01 to 3.24, p-value 0.04). Conclusion: Although ST elevation myocardial infarction admissions decreased after COVID-19 but there was a paradoxical increase in mortality. Late presentation to hospital due to contagion fear, various lockdown measures, unavailability of public transport, economic instability may be some of the contributing factors, in addition to the COVID-19 infection itself, that need to be studied further. [ABSTRACT FROM AUTHOR]

Objective: To determine frequency of cardiac involvement in patients of COVID-19. Secondary objective was to determine association of cardiac involvement with prognosis. Study Design: Descriptive cross-sectional study. Place and Duration of Study: Pak-Emirates Military Hospital, Rawalpindi Pakistan, from Apr to Jul 2020. Methodology: We prospectively assessed the laboratory data, Electrocardiogram and transthoracic echocardiography of all the COVID-19 patients admitted to our institute. Outcomes of interest included length of hospital stay, admission to Intensive Care Unit and mortality. Acute myocardial injury was defined by a value of high-sensitivity troponin I (hs-TnI) above the thth percentile upper reference limit. Statistical Package for the Social Sciences (SPSS) version 23 was used for all the analysis. Results: Our study included 1015 patients, mean age 50.34 (SD 13.71) years, 887 (87.3%) males and 128 (12.6%) females. Three hundred and thirty (n=330, 32.5%) patients had evidence of acute cardiac injury as shown by raised cardiac troponins, but 50, 4.92% had left ventricle dysfunction. Raised cardiac enzymes were associated with marginally prolonged hospital stay (10.03 versus 9.32 days, p-value 0.07) and higher mortality (OR 2.634, confidence interval 1.252-5.543, p-value 0.01). Conclusion: Cardiac involvement is quite common among patients suffering from COVID-19 and predicts worse prognosis. [ABSTRACT FROM AUTHOR]

Objective: To study the frequency, associated risk factors and morphological distribution of Coronary Artery Ectasia (CAE) and Coronary Artery Aneurysm (CAA). Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Cardiology, Armed Forces Institute of Cardiology & National Institute of Heart disease (AFIC/NIHD) Rawalpindi from Jul 2018 to Jul 2019. Methodology: All patients who underwent Primary Percutaneous Coronary Intervention (PCI) for ST elevation Myocardial Infarction (STEMI) at our institute were considered for this descriptive cross sectional study. A consecutive sampling method was used and inclusion/exclusion criteria was applied. Number of patients having ectatic coronary arteries, ectasia distribution and morphological classification was done by trainee researcher after studying the coronary angiograms. Demographic information, symptoms and risk factors were also documented. Data recording, storage, assessment and analysis was done by using SPSS software version 21. Results: A total 1354 patients diagnosed with STEMI underwent PPCI during the study period and Coronary Artery Ectasia (CAE) was diagnosed in 31 patients (2.2%), out of that 5 (16.13%) patients had Coronary Artery Aneurysm (CAA). Mean age of patients was 58.32 (± 11.22). Hypertension was the commonest preexisting risk factor 9 (29%) followed by Diabetes Mellitus (DM) 4 (12.9%). Left Anterior Descending (LAD) artery was ectatic vessel in majority of our study group. Ectatic coronaries were classified as fusiform 20 (64.52%) and saccular 11 (35.48%) on the basis of shape and in type 1-4 (type 1=16.13%, type 2=35.48%, type 3=32.26%, type 4=16.13%). Statistically significant association (p-value=0.003) was found between infarct related artery and the ectatic artery. Conclusion: CAE has low prevalence in STEMI patients but it has statistically significant association with infarct related artery. Hypertension is a common risk factor. Ectasia has a predilection for both LAD and RCA in our study group. [ABSTRACT FROM AUTHOR]

Field experiments were carried out at Mountain Livestock Research Institute (MLRI), Manasbal, Sher-e-Kashmir University of Agricultural Sciences and Technology Kashmir, India to study the direct and residual effect of different rates of organic and chemical sources of nutrients on fodder sorghum-fodder oat cropping sequence during Kharif 2008, 2009 and rabi 2008-09, 2009-10. Application of FYM @ 25tonnes recorded higher green fodder yield of sorghum than rest of treatments. The physical optimum dose of direct+residual effect of FYM on fodder sorghum-fodder oat sequence was 25.49 t ha-1 and economic optimum dose 12.63 t ha-1. Applying 120, 80 and 30 (N, P2O5, K2O kg ha-1) was found superior in green fodder yield than rest of treatments. However, physical optimum dose due to direct +residual effect of N, P2O5 and K2O on fodder sorghum-fodder oat was 134.19, 67.07 and 33.54 kg ha-1 and mean total economic optimum dose was found to be 128.0, 64.19 and 32.62 NPK kg ha-1 respectively. [ABSTRACT FROM AUTHOR]

Hashimoto Encephalopathy (HE) or Steroid-Responsive Encephalopathy associated with Autoimmune Thyroiditis (SREAT) is a rare autoimmune disease characterized by encephalopathy and elevated anti-thyroid antibodies in the absence of a central nervous system (CNS) infection, tumour or stroke. Clinical presentation of HE includes amnestic syndrome, seizures including status epilepticus, ataxia, myoclonus and psychiatric manifestations like depression, mania, psychosis and hallucinations. A good clinical response can be achieved with corticosteroid therapy so early diagnosis and treatment is very beneficial for patients. Here we report four patients with Hashimoto encephalopathy who had neuro-psychiatric manifestations of the disease and had detectable thyroid specific antibodies in the serum (thyroperoxidase antibody formerly known as antimicrosomal antibody). All these patients showed an objectively significant response to methylprednisolone treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy and safety of ketamine (KE) in the management of refractory status epilepticus (RSE) in adults. Study Design: Open Label, unblinded prospective case series. Place and Duration of Study: The study was conducted at Neurology Department Military Hospital Rawalpindi, from Jan 2014 to Dec 2014. Material and Methods: All the patients with status epilepticus, from Jan 2014 to Dec 2014 were treated with ketamine in addition to benzodiazepines, phenytoin and levitricetam. Ketamine was the last drug added and if seizures were still not controlled then anesthetic agents like thiopental and propofol were used. Results: Between Jan 2014 and Dec 2014, twenty patients received IV Ketamine. In 18 patients RSE lasted for more than 24 hours, with a median of 4 days (range 1-8 days). Mean duration of seizures in the study group was 4.45 days (SD 2.01). Ketamine was successful in terminating seizure activity in 40% (n=8) patients while it failed in 15% (n=3) patients. There was additional 15% (n=3) partial response in the form of initial control but these patients had later breakthrough or with drawl seizures. Twenty five percent (n=5) of the patients died during the treatment while in one patient ketamine had to be stopped because of intolerable side effects. In our patients the adverse effects of ketamine included sepsis (35%, 5, n=7), shock (10%, n=2) and pneumonia (10%, n=2). Conclusion: In this small, open-label, unblinded study KE appears effective and safe in treating RSE in adults. Larger, randomized studies will help to confirm data emerging from this preliminary study. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the frequency of different diseases among Pakistani Hajj pilgrims attending the medical facilities of Pakistan Hajj Medical Mission during Hajj 2016 (1437 hijri). Study Design: A descriptive cross sectional study. Place and Duration of Study: Pakistan Hajj Medical Mission hospitals and dispensaries at Makkah Mukkarrmah, Medina Munawwarah and Jeddah, from 10th Aug 2016 to 5th Oct 2016. Material and Methods: All Pakistani Hajj pilgrims reporting to various Pakistan Hajj Medical Mission Hospitals and dispensaries at Makkah, Medina and Jeddah were included in the study. A universal sample of all patients reporting to the Hajj medical mission (A total of 184,496 OPD visits) was used. The patient were initially assessed in Emergency Reception(ER) by medical officers and then referred to respective specialists if required. A specially designed proforma having information regarding name, age, disease and its duration was prepared and filled for each patient separately. A second hospital/dispensary visit of the Hajj pilgrim was considered separately on a new proforma. SPSS version 17 was used to analyze the data. Results: There were a total of 184,496 OPD (Out Patient Department) visits by Pakistani Hajj pilgrims during the study period. Age of the patients ranged from 20-96 years, 74.5% (n=137, 449) were male and 25.5% (n=47047) were female. Number of patients suffering from various diseases and their percentage in order of frequency was; respiratory diseases 29% (n=53187), musculoskeletal disorders 18% (n=33838), gastrointestinal diseases 15% (n=26696), Ear Nose and Throat (ENT) diseases 8% (n=14448), skin disorders 6% (n=10937), eye disease 3% (n=4530), mouth and dental diseases 3% (n=6101), wounds, fractures and burns 3% (n=6186), cardiovascular diseases 2% (n=4433), gynecological disorders 2% (n=4357), infectious disease 1% (n=1055), minor surgeries <1% (n=620), psychiatric disorders <1% (n=40) and other miscellaneous complaints 5% (n=9889). Conclusion: Respiratory illness was the commonest disease among Pakistani Hajj Pilgrims while musculoskeletal and gastrointestinal complaints were also high. This study helps to identify the common diseases encountered during Hajj Medical Mission and may aid in the better preparedness of such missions in future. [ABSTRACT FROM AUTHOR]

Objective: To compare short term mortality in non-diabetic ischemic stroke patients with or without stress hyperglycemia. Study Design: Cohort study. Place and Duration of Study: This study was carried out at Neurology Department of Military Hospital, Rawalpindi from Jan 2010 to Jul 2012 for a total duration of six months. Material and Methods: Non-diabetic ischemic stroke patients were included in the study and they were divided in two groups. Each group had 75 patients. Group 'I' (Normoglycemic or control group) had normal blood glucose level while group 'II' (Hyperglycaemic or cohort) had hyperglycaemia on presentation or over next 72 hours. Prognosis in terms of patient either being dead or alive was determined within or at 4 weeks of admission in both groups. Data were entered and analysed using Statistical Package for Social Sciences SPSS version 10. Descriptive statistics were calculated for both qualitative and quantitative variables. For comparison of short term mortality in hyperglycaemic and normoglycemic stroke patients, chi-square test was applied. p-value <0.05 was considered statistically significant. Results: Short term mortality was higher in cohort (hyperglycemic) group as compared to control (normoglycemic) group (34.7% vs. 14.7%). Relative risk was 2.36. The groups had a statistically significant difference in the short term mortality within four weeks with a Chi-Square 'p' value of 0.004 (p=0.004). Conclusion: Short term mortality in non-diabetic ischemic stroke patients with stress hyperglycemia is higher than those patients who do not have stress hyperglycemia. [ABSTRACT FROM AUTHOR]

The dismal success rate of clinical trials for Alzheimer’s disease (AD) motivates us to develop model systems of AD pathology that have higher predictive validity. The advent of induced pluripotent stem cells (iPSCs) allows us to model pathology and study disease mechanisms directly in human neural cells from healthy individual as well as AD patients. However, two-dimensional culture systems do not recapitulate the complexity of neural tissue, and phenotypes such as extracellular protein aggregation are difficult to observe. We report brain organoids that use pluripotent stem cells derived from AD patients and recapitulate AD-like pathologies such as amyloid aggregation, hyperphosphorylated tau protein, and endosome abnormalities. These pathologies are observed in an age-dependent manner in organoids derived from multiple familial AD (fAD) patients harboring amyloid precursor protein (APP) duplication or presenilin1 (PSEN1) mutation, compared to controls. The incidence of AD pathology was consistent amongst several fAD lines, which carried different mutations. Although these are complex assemblies of neural tissue, they are also highly amenable to experimental manipulation. We find that treatment of patient-derived organoids with β- and γ-secretase inhibitors significantly reduces amyloid and tau pathology. Moreover, these results show the potential of this model system to greatly increase the translatability of pre-clinical drug discovery in AD. [ABSTRACT FROM AUTHOR]

Collagen and silk materials, in neat forms and as silica composites, were flown for 18 months on the International Space Station [Materials International Space Station Experiment (MISSE)-6] to assess the impact of space radiation on structure and function. As natural biomaterials, the impact of the space environment on films of these proteins was investigated to understand fundamental changes in structure and function related to the future utility in materials and medicine in space environments. About 15% of the film surfaces were etched by heavy ionizing particles such as atomic oxygen, the major component of the low-Earth orbit space environment. Unexpectedly, more than 80% of the silk and collagen materials were chemically crosslinked by space radiation. These findings are critical for designing next-generation biocompatible materials for contact with living systems in space environments, where the effects of heavy ionizing particles and other cosmic radiation need to be considered. [ABSTRACT FROM AUTHOR]

MTLn3 cells derived from mouse mammary epithelium are known to be highly malignant and are resistant to both radio- and chemo-therapy. We exposed MTLn3 cells to various doses of inorganic Arsenic trioxide (As2O3) in combination with ionizing radiation. Cells were treated with a series of As2O3 concentrations ranging from 20 μM to 1.22 nM for 8 hour, 24 hour and 48 hour periods. Post-treated cell proliferation was quantified by measuring mitochondrial activity and DNA analysis. Cells exposed to radiation and As2O3 at concentration greater than 1.25 μM showed apoptosis and radiations alone treated cells were statistically not different from the control. Hormesis was observed for As2O3 concentrations in the range of 0.078 μM to 0.625 μM while the combined chemo and radiation treatments of the cells did not affect the hormetic effect. We have demonstrated that As2O3 (in the presence and absence of ionizing radiation) in specific low concentrations induced apoptosis in the otherwise chemoresistant cancer cells. This low concentration-mediated cell death is immediately followed by a surge in cell survival. Low dosing dosimetry is highly desirable in metronomic therapy however, it has a narrow window since necrosis, hormesis, apoptosis and other dose-dependent biological processes take place in this region. Further quantifiable dosimetry is highly desired for routine clinical practice. [ABSTRACT FROM AUTHOR]

In the last decades, the use of insecticides in agriculture for selective control of pests has become crucial. Researches have produced a diverse range of products with novel modes of action. However, the extensive use of these compounds in the agriculture system raises public concern, because of the harmful potential of such substances in the environment and human health.When Endosulfan, an organochlorine insecticide, (0-400ppm), was added to an exponentially growing medium and the effects on Azolla microphylla were followed for 6 days, the following observations were made: Dry weight, Root number, root length, total chlorophyll and Carotenoid content decreased as compared to the control. Carotenoid content decreased more than chlorophyll content. These changes paralleled the inhibition of the rate of net photosynthesis, suggesting that the photosynthetic apparatus is one of the primary targets of the insecticide action. Insecticide exposure resulted in the reduction of relative growth rate at all the applied dose concentrations. An increase in the doubling time was also noticed which is an indication of delayed growth. Furthermore, Endosulfan induced the formation of MDA indicating enhanced Lipid peroxidation. Overall the effect of endosulfan was dose dependent. Since plants are sessile organisms and have limited mechanisms for insecticide application avoidance they need flexible means for acclimatization to changing environmental conditions. Hence in order to improve a plant protection, this kind of researches may be fruitful in understanding of mechanisms contributing to effect of endosulfan on plant system. [ABSTRACT FROM AUTHOR]

Abstract: The recreation of an in vitro microenvironment to understand and manipulate the proliferation and migration of invasive breast cancer cells may allow one to put a halt to their metastasis capacity. Invasive cancer cells have been linked to embryonic stem (ES) cells as they possess certain similar characteristics and gene signatures. Embryonic microenvironments have the potential to reprogram cancer cells into a less invasive phenotype and help elucidate tumorigenesis and metastasis. In this study, we explored the feasibility of reconstructing embryonic microenvironments using mouse ES cells cultured in alginate hydrogel and investigated the interactions of ES cells and highly invasive breast cancer cells in 2D, 2&1/2D, and 3D cultures. Results showed that mouse ES cells inhibited the growth and tumor spheroid formation of breast cancer cells. The mouse ES cell microenvironment was further constructed and optimized in 3D alginate hydrogel microbeads, and co-cultured with breast cancer cells. Migration analysis displayed a significant reduction in the average velocity and trajectory of breast cancer cell locomotion compared to control, suggesting that bioengineered mouse ES cell microenvironments inhibited the proliferation and migration of breast cancer cells. This study may act as a platform to open up new options to understand and harness tumor cell plasticity and develop therapeutics for metastatic breast cancer. [Copyright &y& Elsevier]

Cisplatin or cis-diamminedichloroplatinum (CDDP) is the first member of a class of platinum-containing anti-cancer drugs that act by binding to and causing cross-linking of deoxyribonucleic acid, which ultimately triggers apoptosis. Cisplatin has a broadspectrum antineoplastic activity against various types of human tumors. Unfortunately, the optimal usefulness of Cisplatin is limited secondary to its dose related toxicity especially nephrotoxicity. Cisplatin chemotherapy is also associated with cardiotoxic effects that may range from silent arrhythmias to heart failure and even sudden cardiac death. These effects are more pronounced when cisplatin is combined with other cardiotoxic drugs. Here, we report a case of patient of cancer lung who developed paroxysmal supraventricular tachycardia following administration of Cisplatin. A brief review of the literature follows. [ABSTRACT FROM AUTHOR]

Objective: To study the HRCT chest findings in patients undergoing cardiac interventions during COVID-19 era. Study Design: Cross sectional analytical study. Place and Duration of Study: Armed Forces Institute of Cardiology & National Institute of Heart Disease (AFIC/NIHD) Rawalpindi, from Apr 2020 to May 2020. Methodology: All the admitted cardiac patients who were to undergo any invasive cardiac intervention underwent plain HRCT chest and polymerase chain Reaction (PCR) for SARS-CoV-2 simultaneously. One hundred and ten patients were studied. We analyzed preexisting respiratory illnesses, clinical, echocardiographic and radiological features. Data recording, storage, assessment and analysis was done by using SPSS-21. Results: Our study included 110 patients (87 Male, 23 Female, median age 52 Years). Common reasons for admission were coronary angiography 43 (39.1%), acute Left Ventricular Failure (LVF) 30 (27.3%), Percutaneous Coronary Intervention (PCI) 13 (11.8%) and chest pain evaluation 10 (9.1%). Cardiomegaly (29.1%) followed by consolidation (9.1%) were commonest radiological finding. Two third patients had abnormal HRCT chest but only few had radiological findings either suspicious (6.4%) or indeterminate (11.8%) for COVID-19. Respiratoy symptoms, positive PCR for COVID-19 and severe Left ventricular dysfunctions were correlated with abnormal HRCT findings, correlation being statistically significant (p-value <0.05). Conclusion: HRCT chest is a non-invasive and highly sensitive imaging modality, which can rapidly help in identifying, and isolating suspected cases of novel corona virus as well as in diagnosing unknown pre-existing lung diseases in cardiac patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the relative diagnostic efficacy of ultrasonography versus Magnetic Resonance Cholangiopancreatography for the diagnosis of common duct stones. Study Design: Prospective observational study. Place and Duration of Study: Armed Forces Institute of Radiology & Imaging (AFIRI) Rawalpindi, from Jun 2017 to Jun 2018. Methodology: All the patients with the suspicion of common bile duct stones during the study period were included in the study. All study patients underwent abdominal ultrasonography, Magnetic Resonance Cholangio Pancreatography and Endoscopic Retrograde Cholangiopancreatography. Results: A total of one hundred and thirty-four patients were included in this study. There were stones in common duct in 101 (75%) cases using Endoscopic Retrograde Cholangiopancreatography as gold standard. Ultrasonography indicated stones in 79 (78.2%) while Magnetic Resonance Cholangio Pancreatography diagnosed stones in 93 (92%) patients. The diagnostic accuracy of ultrasonography and Magnetic Resonance Cholangio Pancreatography 70.50% and 92.4% respectively. Conclusion: Magnetic Resonance Cholangio Pancreatography is an accurate and sensitive diagnostic modality as compared to USG so it should be the logical next investigation if clinical suspicion remains high. [ABSTRACT FROM AUTHOR]

Objective: To determine prevalence, clinical patterns and outcomes of neurological involvement in a cohort of primary sjogren’s syndrome (PSS) patients presenting to a tertiary care hospital. Study Design: Observational retrospective cross-sectional case-control study. Place and Duration of Study: This study was carried out at Neurology department of Pak Emirates Military Hospital, Rawalpindi, from May 2015 to Jun 2016. Patients and Methods: All patients fulfilling American College of Rheumatology (ACR) criteria of PSS and having neurological involvement, who were admitted in Neurology wards from May 2015 to June 2016, were included in the study. Demographic, clinical and seroimmunological data of the patients was documented. Results: A total of 26 patients with PSS had some degree of neurological involvement. Mean age was 40.50 years. (SD 14.803, min 22, max 78). Fifteen patients were female and 11 were male. Sicca symptoms (ocular and oral dryness) were present in 38.5%. Serological marker anti Ro and La were present in 76.9% and 42.3% respectively while both Ro and La were present in 34.6%. Lip biopsy was diagnostic in 80.8% and schirmer test was positive in 46.2%. Refractory headache was present in 84.6%. Seizures occurred in 34.6%, which were focal in 23.1% and generalized in 11.5%. Trigeminal neuralgia was present in 26.9%, multiple cranial nerve palsies in 15.4% and recurrent facial nerve palsies in 11.5%. Optic neuritis was seen in 19.2%. Clinical presentation mimicking relapsing and remitting multiple sclerosis was seen in 30.8% of patients among whom 61.5% also met revised McDonald criteria for dissemination in space (DIS) on MRI and 23.1% met criteria for dissemination in time. MRI brain showed cortical lesions in 42.3%. Longitudinally extensive transverse myelitis involving cervical and upper thoracic cords was present in 26.9% of patients. Conclusion: The diagnosis of neuro-sjogren’s syndrome (NSS) can be difficult in the absence of sicca symptoms especially when neurological manifestations precede sicca symptoms by many years. This requires a high index of clinical suspicion and low threshold for investigations like lip biopsy and autoantibody profile for the diagnosis. This study highlights the need to revise the overemphasis of sicca symptoms in various current diagnostic criteria in order to improve early recognition and initiation of treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of different causative bacteriological organisms and their antibiotic sensitivity from Endotracheal Aspirate (EA) of patients suffering from Ventilator Associated Pneumonia (VAP). Study Design: Prospective cross sectional study. Place and Duration of Study: Intensive Care Unit (ICU), Combined Military Hospital (CMH) Lahore, from May 2013 to Nov 2013. Material and Methods: A total of 180 cases of VAP, fulfilling the ınclusion criteria and admitted in the ICU, were included in the study using the non-probability consective sampling technique. A written informed consent was obtained from the family. All these patients underwent endotracheal aspirate for microscopy and culture. Antibiotic sensitivity was determined using standard antibiotics regimens. Results: Out of 180 patients, 165 (91.7%) were culture positive while 15 (8.3%) were culture negative. Gramnegative bacilli accounted for about 70% of all isolates. The most common organism isolated was Pseudomonas aeruginosa 25% (n=45) followed by MRSA 18.9% (n=34), Klebsiella 15.6% (n=28), Actinobacter spp 13.3% (n=24), E.coli 11.7% (n=21) and Citrobacter spp 4.4% (n=8). Carbapenem was the most sensitive drug that was seen in our setup but still 43.9% of the isolates showed resistance against it and resistance was noted still higher with Actinobacter spp, where 83% isolates were resistant. Quinolones showed resistance in 100% of the isolates of Actinobacter, MRSA and Citrobacter. While more than 50% strains of Pseudomonas, E.coli and Klebsiella were also resistant to quinolones. Cephalosporins showed excellent sensitivity towards gram negative bacteria which included Citrobacter (100% sensitive) and E.coli (80% sensitive). Polymxins showed more than 50% sensitivity to Pseudomonas aeruginosa, Actinobacter, E. coli and Klebsiella. Conclusion: VAP remains a very important hospital-acquired infection. The most prevalent etiological organism in our study was Pseudomonas aeruginosa and the most effective antibiotics were carbapenems. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of non-invasive hepatic ultrasound score for the diagnosis of non-alcoholic fatty liver disease (NAFLD) by keeping computed tomography. (CT) as the gold standard. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging Rawalpindi from Dec 2017 to May 2018. Methodology: All patients from any ethnicity and gender with more than 18 and less than 60 years of age were considered for the study. Hepatic ultrasound score based on the anteroposterior diameter of the right lobe of the liver, deep beam attenuati on was calculated, and results were compared with CT scan findings. Results: A total of 101 patients were included. A total of 69 patients had a total Ultrasound score of 2 or more, fulfilling the study's criteria to be labelled as Non-Alcoholic Fatty Liver Disease. On a CT scan, 71 patients fulfilled the criteria to be labelled as having Non-Alcoholic Fatty Liver Disease. Keeping the Computed Tomography scan gold standard, 59 patients were true positive, and 10 were false positive. The sensitivity and specificity of this score were 83.09 % and 66.67%, respectively. The hepatic ultrasound score had a Positive Predictive Value of 85.50% and a Negative Predictive Value of 62.5%. Conclusion: Ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe is a reliable, reproducible and accurate tool for diagnosing Non-Alcoholic Fatty Liver Disease. [ABSTRACT FROM AUTHOR]

Objective: To share our experience of percutaneous trans-catheter aortic valve implantation in patients with severe symptomatic aortic stenosis. Study Design: A retrospective cross sectional study. Place and Duration of Study: The study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC/NIHD) Rawalpindi, from Mar 2015 to Feb 2020. Methodology: Retrospective analysis of all consecutive patients who underwent percutaneous trans-catheter aortic valve implantation was done to assess its immediate, short and long term outcome and safety. Twenty patients have undergone trans-catheter aortic valve implantation since 2015 in the institute. Base line blood chemistry including creatinine clearance, ultra-sonography abdomen, carotid Doppler, chest X-ray, High-Resolution Computed Tomography chest was done in all cases as part of the protocol. Mean age of the patients was 73 ± 7.91. There were sixteen males (80.0%) and four females (20.0%). All patients under went procedure through transfemoral route. Valve structure and peripheral vasculature for suitability of the procedure was assessed by computerized coronary tomographic angiography with TAVI protocol. In eleven patients aortic valve was trileaflet (55.0%) and in remaining nine it was bicuspid (45.0%). Mean gradient across the valve pre-procedure was 56.37 ± 9.14. Thirteen patients (65.0%) presented with angina/dysnoea NYHA III, 6 patients with syncope (30.0%) and one (5.0%) had heart failure. Two patients had undergone previous coronary artery bypass surgery. Procedure was carried out under general anesthesia in all patients except one. Balloon expandable Edwards Sapienvalve was implanted in two patients and self-expandable Core Valve/Evolut R in eighteen patients. Results: Seventeen patients underwent the procedure successfully with reduction of the mean gradients immediately after valve implantation to less than 15 mmHg recorded in the cath labangiographically subsequently complemented by transthoracic echocardiography. There were 3 deaths during the index hospitalization. Two occurred in the catheterization laboratory, one death was due to development of severe acute aortic regurgitation and second was due to acute coronary obstruction. Third death occurred due to acute kidney injury after seven days. Five patients died in next three months during follow up. One patient required permanent pacemaker because of development of left bundle branch block and second degree atrio-ventricular block post procedure. Conclusion: Transcatheter aortic valve implantation in patients with severe symptomatic aortic stenosis is a very effective and procedurally safe option and reasonable alternative to surgical valve replacement in high operative risk individuals. [ABSTRACT FROM AUTHOR]

Objective: To determine the efficacy and safety of electroconvulsive therapy (ECT) for the management of neuroleptic malignant syndrome (NMS) in adults. Study Design: Open label, unblinded series. Place and Duration of Study: This study was carried out at the Department of Neurology, Military Hospital Rawalpindi, from Jan 2015 to Dec 2015. Material and Methods: All the patients with the diagnosis of NMS during the study period were included in the study. Consective non-probability sampling technique was used. Patients were divided into two groups; uncomplicated and complicated cases of NMS. Results: A total of nineteen patients were included in this pilot study. Out of all, thirteen (68.4%) were males and six (31.6%) were females. Mean age of the patients was 35.05 (SD 13.362) years. The drug classes causing NMS were antipsychotic medicines in 73.7% of patients and antiemetics in 26.3% of patients. Mean electroconvulsive therapy (ECT) sessions given were 6.16 (SD 2.062). Following treatment n=16 (84.2%) patients had complete recovery while n=3 (15.3%) patients died. Conclusion: In this small, open label, unblinded study ECT appears effective and safe in treating NMS in adults. Larger randomized studies will help to confirm data emerging from this preliminary study. [ABSTRACT FROM AUTHOR]

Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cydin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders, including Alzheimer's disease. Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double-transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice. We observed significant reduction of phosphorylated tau and its seeding activity in the brain of double transgenic mice compared with the P301S mice. Furthermore, synaptic loss and impaired LTP at hippocampal CA3 region of P30IS mice were attenuated by blocking p25 generation. Tofurther validate the role of p25/Cdk5 in tauopathy, we used frontotemporal dementia patient-derived induced pluripotent stem cells (iPSCs) carrying the Tau P301L mutation and generated P301L: Δp35KI isogenic iPSC lines using CRISPR/Cas9 genome editing. We created cerebral organoids from the isogenic iPSCs and found that blockade of p25 generation reduced levels of phosphorylated tau and increased expression of synaptophysin. Together, these data demonstrate a crucial role for p25/Cdk5 in mediating tau-associated pathology and suggest that inhibition of this kinase can remedy neurodegenerative processes in the presence of pathogenic tau mutation. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of non-invasive hepatic ultrasound score for the diagnosis of non-alcoholic fatty liver disease (NAFLD) by keeping computed tomography. (CT) as the gold standard. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Radiology and Imaging Rawalpindi from Dec 2017 to May 2018. Methodology: All patients from any ethnicity and gender with more than 18 and less than 60 years of age were considered for the study. Hepatic ultrasound score based on the anteroposterior diameter of the right lobe of the liver, deep beam attenuati on was calculated, and results were compared with CT scan findings. Results: A total of 101 patients were included. A total of 69 patients had a total Ultrasound score of 2 or more, fulfilling the study's criteria to be labelled as Non-Alcoholic Fatty Liver Disease. On a CT scan, 71 patients fulfilled the criteria to be labelled as having Non-Alcoholic Fatty Liver Disease. Keeping the Computed Tomography scan gold standard, 59 patients were true positive, and 10 were false positive. The sensitivity and specificity of this score were 83.09% and 66.67%, respectively. Th e hepatic ultrasound score had a Positive Predictive Value of 85.50% and a Negative Predictive Value of 62.5%. Conclusion: Ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe is a reliable, reproducible and accurate tool for diagnosing Non-Alcoholic Fatty Liver Disease. [ABSTRACT FROM AUTHOR]

Electric field is known as an important regulator to guide the development and regeneration of many tissues. The aim of this study was to investigate the osteogenic differentiation potential of human mesenchymal stem cells (hMSCs) cultivated on silk-fibroin films in response to different parameters, i.e. frequency, voltage, distance between electrodes, and/or culture conditions (growth medium or osteogenic medium). Silk films were prepared in the presence of platinum wires to study the impact of exogenous electrostimulation on the cells for up to 14 days. The experimental groups can be defined as high voltage in osteogenic differentiation medium, low voltage in osteogenic differentiation medium, and low voltage in growth medium in this study. Compared to the unstimulated controls (silk films without platinum wires), low voltage (10 mV) did not influence proliferation, while it enhanced osteogenic differentiation according to early and late osteogenic markers in osteogenic differentiation medium. In growth medium, low voltage increased cell proliferation in contrast to osteogenic medium. On the other hand, high voltage (500 mV) stimulated cell proliferation and only late osteogenic markers in osteogenic medium. The results suggest the potential to exploit exogenous biophysical control of cell functions towards tissue-specific goals. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of adding body mass index and neck circumference to Epworth Sleepiness Scale (ESS) for diagnosing obstructive sleep apnea hypopnea syndrome in sleep clinics. Study Design: Cross sectional validation study. Place and Duration of Study: Department of Pulmonology, Military Hospital Rawalpindi from 1st July 2013 to 01 September 2014. Material and Methods: The ESS and ESS plus body mass index (BMI) and neck circumference (NC) data was evaluated for 150 patients hospitalized in our hospital for polysomnographic evaluation of obstructive sleep apnea. Overnight polysomnography (PSG) was done for all patients and was considered the gold standard for diagnosis of OSA. ESS Scoring, BMI and NC data was done using pre-designated questionnaire. All the data was analyzed using SPSS version 19. Results: Age ranged from 18-74 years with mean age of the study group 53 (±12.1 SD) years. Out of study population 87 (58%) were males and 63 (42%) females. In study population 80 (55.3%) patients had ESS >10. while 102 patients had ESS>10 with BMI > 35 kg/m2 and NC>40 cm. Using an AHI = 5 for OSA, 136 patients (90.6%) had OSA. Sensitivity of ESS > 10 for OSA was 55.15 % but increased to 72.79% when BMI > 35 kg/m2 and NC > 40 cm was added to patients with ESS > 10. Similarly specificity and predictive values of study population for diagnosing OSA also increased after adding BMI and NC to ESS. Conclusions: In this study adding body mass index (BMI) and NC to ESS score significantly increased the sensitivity and specificity and positive predictive value for diagnosis of OSA. [ABSTRACT FROM AUTHOR]

Diabetic myonecrosis is a rare and underdiagnosed complication of long-standing, uncontrolled diabetes. It usually occurs in patients with long-standing diabetes in the presence of microvascular complications. Thigh muscles are more commonly affected and the usual presentation is thigh swelling with or without pain, systemic features being rare. Magnetic resonance imaging is the gold standard for diagnosis. Most patients recover spontaneously with bed rest, adequate analgesia and good glycemic control. We present a case of recurrent myonecrosis of adductor muscles of the thigh in a patient with long standing type 2 diabetes mellitus who recovered with conservative management. [ABSTRACT FROM AUTHOR]

Highlights: [•] Polycrystalline CdS thin films are fabricated by means of Close Spaced Sublimation technique. [•] Ag is doped by simple ion-exchange technique in order to reduce resistivity of CdS thin films. [•] Remarkable reduction in resistivity without introducing many transparency losses. [ABSTRACT FROM AUTHOR]

Aim : To evaluate the effects of chlorpyriphos, lead acetate, vitamin C alone, and in combination on the activity of oxidative stress parameters in wistar rats. Marerial and Methods: Rats of 150-200g body weight were divided into eight groups of six animals each and were subjected to various daily oral treatment regimes for 98 days. Group I served as control receiving only corn oil, group II received chlorpyriphos @ 5.5 mg/ kg in corn oil, group III received lead acetate @100 ppm in water, whereas animals in group IVth received a combination of chlorpyriphos @ 5.5mg/kg in corn oil and lead acetate @ 100 ppm in water. Group Vth received vitamin C @ 100mg/kg in water, group VIth received a combination of chlorpyriphos @ 5.5mg/kg and vitamin C @ 100mg/kg , group VIIth received lead acetate @ 100 ppm in water and vitamin C @ 100mg/kg and group VIIIth received chlorpyriphos @ 5.5mg/kg , lead acetate @100ppm in water and vitamin C @ 100mg/kg. Results: Administration of both chlorpyriphos and lead acetate caused a significant decrease in oxidative stress parameters viz. blood glutathione, catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase (GST) along with a significant increase in lipid peroxidation level when given alone or in combination. Conclusions: The study demonstrated that treatment of chlorpyriphos and lead treated rats with vitamin C significantly improved some of altered oxidative stress parameters revealing the protective effect of this vitamin C against oxidative stress induced by chlorpyriphos and lead. [ABSTRACT FROM AUTHOR]

Higher demand and cost of labor and water shortage have forced the farmers to look for an alternate method of cultivation in rice as a substitute to the existing conventional transplanting. Dry direct seeding and water seeding have emerged as better alternatives over transplanting method. These methods not only result in labor saving, but also result in significant water saving in rice. These are important adaptation strategies to the impending climate change. However, the direct seeding method is confronted with severe weed infestation and yield losses if weeds are not managed well. Against this backdrop, a field study was undertaken during kharif seasons of 2019 and 2020 to evaluate the effect of crop establishment methods and weed management practices on rice and its associated weed flora. The results demonstrated that grain yields obtained under water seeding (WS) were statistically at par with transplanting (CT), but significantly superior to dry direct seeding (DDSR). Yield attributes were significantly superior in WS as compared DDSR, but were at par with CT. Weed density followed the order of DDSR > WS > CT. With the advancement in age of the crop, sedges dominated in DDSR, whereas broad-leafweeds (BLW) dominated in WS and CT methods of establishment. All the herbicides reduced the weed density significantly as compared to weedy check. Penoxulam (PE) reduced the weed density and weed dry matter on an average by 91% and 92% at 30 DAS/DAT over weedy check, respectively. PE proved significantly superior in controlling all the sedges and grasses but was less effective against BLW. Maximum reduction in yield due to weeds was observed in weedy check (WC) (58%) and the lowest was observed in PE (3%). Application of PE @ 22.5 g ha−1 under the WS method of crop establishment resulted in highest average weed control efficiency and grain yield. [ABSTRACT FROM AUTHOR]

Summary The apolipoprotein E4 ( APOE4 ) variant is the single greatest genetic risk factor for sporadic Alzheimer’s disease (sAD). However, the cell-type-specific functions of APOE4 in relation to AD pathology remain understudied. Here, we utilize CRISPR/Cas9 and induced pluripotent stem cells (iPSCs) to examine APOE4 effects on human brain cell types. Transcriptional profiling identified hundreds of differentially expressed genes in each cell type, with the most affected involving synaptic function (neurons), lipid metabolism (astrocytes), and immune response (microglia-like cells). APOE4 neurons exhibited increased synapse number and elevated Aβ 42 secretion relative to isogenic APOE3 cells while APOE4 astrocytes displayed impaired Aβ uptake and cholesterol accumulation. Notably, APOE4 microglia-like cells exhibited altered morphologies, which correlated with reduced Aβ phagocytosis. Consistently, converting APOE4 to APOE3 in brain cell types from sAD iPSCs was sufficient to attenuate multiple AD-related pathologies. Our study establishes a reference for human cell-type-specific changes associated with the APOE4 variant. Video Abstract [ABSTRACT FROM AUTHOR]